Influenza is an acute respiratory illness of global importance in humans and animals (both domesticated and wild) including, but not limited to, horses, pigs, chickens, ducks, turkeys, ferrets, and wild birds. Virulent and lethal outbreaks of influenza continue to threaten global health. As demonstrated by the H1N1 influenza pandemic of 2009, researchers, government officials, and medical practitioners are acutely aware of the continuing threat of pandemics of virulent and lethal influenza requiring new methods of treatment and novel therapeutic compounds. Researchers, government officials, and medical practitioners have also believed, however, it was not possible to develop long term therapies against influenza viruses across strains and across time because the influenza virus is subject to such rapid mutation as it moves through a population (and subject to hosting in a large variety of non-human reservoirs), such that an effective therapy for one year in a particular strain is not expected to be effective in the years to come against that strain or against other strains of influenza virus. Researchers, government officials, and medical practitioners have nevertheless long understood that a therapy against influenza that could be applied across strains and/or across time would be immensely helpful in attacking the global threat of influenza. Such a therapy was simply not considered possible until now.
As such, until now, influenza vaccines have remained the most effective defense against influenza virus. However, because of the ability of the virus to mutate, and the availability of non-human host reservoirs, influenza has continued to remain an emergent or re-emergent infectious threat.
Traditionally, vaccines have been developed on a twice-yearly basis, based on post hoc hematological classification of the increasing number of emerging influenza virus strains. As such, the only basis for annual classification of influenza virus as present or absent in a given year was identification by serological testing of the hemagglutinin and neuraminidase proteins in an isolate of virus. The activity of a strain of influenza was, as a result, only recorded after the occurrence of an outbreak, never in advance.
Because of the delay inherent in traditional methods of surveillance, presently applied technology does not allow for the design of effective vaccines early in an outbreak and has not allowed for the design of vaccines that might apply to more than one outbreak over time or across strains. Furthermore, presently applied vaccine production technology delays the availability of vaccines even after an outbreak occurs since many months are needed for production of vaccines following vaccine design. As previous and current events make clear (such as the current H1N1 influenza pandemic of 2009), despite the best intentions of the vaccine industry, current biological technology cannot supply all of the world's 6 billion people and billions of animals in a timely manner with vaccines against emerging diseases. That is, using currently applied technology, vaccines against emerging diseases are not produced prior to global outbreak of the disease and often are not produced until the emerging disease outbreak has subsided.
The applicants' discovery of Replikin chemistry in the virus genome structure, however, now provides methods of predicting future outbreaks of strains of influenza virus and now provides methods of identifying conserved targets in emerging strains of influenza against which vaccines may be developed prior to or at the outset of an outbreak. Such vaccine development can be undertaken in as few as seven days.
When an outbreak of influenza is identified, one aspect of the outbreak that is useful to public health researchers and government officials is a differentiation of the infectivity and the lethality of the influenza virus strain that is the agent of the outbreak. An influenza virus strain that is both relatively more infective and relatively more lethal is an influenza strain that will likely cause increased morbidity and mortality in an outbreak. When public health researchers and government officials have advanced knowledge of the infectivity and lethality of an influenza strain, they have crucial additional time for preparations of vaccines and other health measures in advance of a spreading outbreak. Early differentiation of infectivity and lethality of a strain of influenza that is causing an outbreak is of significant importance and utility to those coordinating a response to the outbreak and to those designing vaccines and other health measures in response to an outbreak. For example, early differentiation of infectivity and lethality of a strain of influenza virus causing an outbreak allows for a design of therapies that target the infectivity of a virus, the lethality of a virus, or both,
There is a continuing need in the art for quantitative methods of differentiating, preventing, and treating outbreaks caused by virulent strains of influenza. Because of the annual administration of influenza vaccines and the short period of time when a vaccine can be administered, strategies directed at improving vaccine coverage are of critical importance. There is additionally a continuing need in the art for therapies against influenza virus that apply across strains and across time.
Replikin peptides are a family of small peptides that have been correlated with the phenomenon of rapid replication in influenza, malaria, West Nile virus, foot and mouth disease, and many other pathogens. Replikin peptides have likewise been generally correlated with the phenomenon of rapid replication in viruses, organisms, and malignancies.
Identification of Replikin peptides has provided targets for detection and treatment of pathogens, including vaccine development against virulent pathogens such as influenza virus, malaria, West Nile virus, and foot and mouth disease virus. In general, knowledge of and identification of this family of peptides enables development of effective therapies and vaccines for any pathogen that harbors Replikins. The phenomenon of the association of Replikins with rapid replication and virulence has been fully described in U.S. Pat. No. 7,189,800; U.S. Pat. No. 7,176,275; U.S. Pat. No. 7,442,761; and U.S. application Ser. No. 11/355,120. Both Replikin concentration (number of Replikins per 100 amino acids) and Replikin composition have been correlated with the functional phenomenon of rapid replication.
There is a continuing need for monitoring Replikin sequences in strains of influenza virus to identify compounds for therapies that respond to influenza mutations. There is also a need to develop Replikin-based therapies that are effective across strains and within strains as they mutate over time. There is an additional need to develop Replikin-based therapies that are active against the infectivity of influenza viruses and/or that are active against the lethality of influenza viruses.